Interpretive Summary: The hypothesized interplay between endogenous and exogenous retroviruses leading to integration of retroviral DNA into the genomic DNA of sheep was studied. Retroviruses can become integrated into the genomic DNA of the host and these “endogenous” retroviruses may protect against related exogenous retroviruses that are pathogenic. Thus, a symbiotic relationship may favor integration of retroviruses into host DNA. This study of 27 endogenous retroviruses supports the concept that coadaptive genetic changes occurred between endogenous and exogenous retroviruses of sheep. The discovery of a rare endogenous retrovirus that likely integrated after establishment of the Texel breed suggests that exogenous retroviruses are still being incorporated into genomic DNA of domesticated sheep.

Technical Abstract:
Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections of the host germline transmitted vertically from generation to generation. It is hypothesized that during evolution some ERVs were used by the host to drive extinction of exogenous horizontally-transmitted retroviruses. Several mechanisms of ERVs-mediated viral interference have been described especially in laboratory animal species; however, data suggesting that these mechanisms have influenced the coevolution of endogenous/exogenous retroviruses and their hosts have been more difficult to obtain. Sheep are an interesting model organism to study retrovirus-host coevolution because two exogenous (i.e., horizontally transmitted) oncogenic retroviruses, jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV), coexist with highly related endogenous retroviruses (enJSRVs) some of which have dominant negative properties.